Solid freeform fabrication (“SFF”) is the name given to a class of manufacturing methods which allow the fabrication of three-dimensional structures directly from computer-aided design (“CAD”) data. SFF processes are generally additive, in that material is selectively deposited to construct the product rather than removed from a block or billet. Most SFF processes are also layered, meaning that a geometrical description of the product to be produced is cut by a set of parallel surfaces (planar or curved), and the intersections of the product and each surface—referred to as slices or layers—are fabricated sequentially. Together, these two properties mean that SFF processes are subject to very different constraints than traditional material removal-based manufacturing. Nearly arbitrary product geometries are achievable, no tooling is required, mating parts and fully assembled mechanisms can be fabricated in a single step, and multiple materials can be combined, allowing functionally graded material properties. New features, parts, and even assembled components can be “grown” directly on already completed objects, suggesting the possibility of using SFF for the repair and physical adaptation of existing products. On the other hand, a deposition process must be developed and tuned for each material, geometry is limited by the ability of the deposited material to support itself and by the (often poor) resolution and accuracy of the process, and multiple material and process interactions must be understood.
SFF has traditionally focused on printing passive mechanical parts or products in a single material, and the emphasis of research has been on developing new deposition processes (U.S. Pat. No. 5,121,329 to Crump; U.S. Pat. No. 5,134,569 to Masters; U.S. Pat. No. 5,204,055 to Sachs et. al.; and U.S. Pat. No. 5,126,529 to Weiss et. al.), on improving the quality, resolution, and surface finish of fabricated products, and on broadening the range of single materials which can be employed by a given SFF process, including biocompatible polymers and other biomaterials (Pfister et al., “Biofunctional Rapid Prototyping for Tissue-engineering Applications: 3D Bioplotting Versus 3D Printing,” Journal of polymer Science Part A: Polymer Chemistry 42:624-638 (2004); Landers et al., “Desktop Manufacturing of Complex Objects, Prototypes and Biomedical Scaffolds by Means of Computer-assisted Design Combined with Computer-guided 3D Plotting of Polymers and Reactive Oligomers,” Macromolecular Materials and Engineering 282:17-21 (2000)), and living cells (Roth et al., “Inkjet Printing for High-throughput Cell Patterning,” Biomaterials 25:3707-3715 (2004)). These improvements have allowed freeform fabrication to become a viable means of manufacturing finished functional parts, rather than only prototypes.
More recently, the greater utility of freeform fabricated products having multiple materials has been recognized, prompting reexamination and novel research into processes which can fabricate using multiple materials (U.S. Pat. No. 5,260,009 to Penn), and which can thereby produce complex articles with a variety of functionality, including functionally graded materials (Ouyang et al., “Rapid Prototyping and Characterization of a WC-(NiSiB Alloy) Ceramet/Tool Steel Functionally Graded Material (FGM) Synthesized by Laser Cladding,” Columbus, Ohio, USA: TMS—Miner. Metals & Mater. Soc. (2002); Smurov et al., “Laser-assisted Direct Manufacturing of Functionally Graded 3D Objects by Coaxial Powder Injection,” Proceedings of the SPIE—The International Society for Optical Engineering 5399:27 (2004)), electronics, MEMS (Fuller et al., “Ink-jet Printed Nanoparticle Microelectromechanical Systems,” Journal of Microelectromechanical Systems 11:54-60 (2002)), living tissue constructs (Mironov et al., “Organ Printing: Computer-aided Jet-based 3D Tissue Engineering,” Trends in Biotechnology 21:157-161 (2003)), and compositions of living and nonliving materials (Sun et al., “Multinozzle Biopolymer Deposition for Tissue Engineering Application,” 6th International Conference on Tissue Engineering, Orlando, Fla. (Oct. 10-13, 2003); International Patent Application No. PCT/US2004/015316 to Sun et al.; and U.S. Pat. No. 6,905,738 to Ringeisen et al.). All of these systems still depend upon a small fixed set of deposition process technologies, and are therefore limited to the materials which can be adapted to those processes, by the effects of those particular processes on the materials, and by the fabrication rates and resolutions of those processes. In particular, the system of U.S. Pat. No. 6,905,738 to Ringeisen et al., requires that for every material to be deposited, a two material system be developed comprising the material to be transferred, and a compatible matrix material which is vaporized by the laser in order to propel the transfer material to the substrate. In addition, this system has only demonstrated fabrication of thin films of materials—its ability to deposit many layers of materials is not well established. The system and method of Sun et al., “Multinozzle Biopolymer Deposition for Tissue Engineering Application,” 6th International Conference on Tissue Engineering, Orlando, Fla. (Oct. 10-13, 2003) and International Patent Application No. PCT/US2004/015316 to Sun et al., is limited to a fixed set of four deposition processes and requires that the alginate materials be deposited into a bath of liquid crosslinking agent—a limitation it shares with the work of Pfister et al., “Biofunctional Rapid Prototyping for Tissue-engineering Applications: 3D Bioplotting Versus 3D Printing,” Journal of Polymer Science Part A: Polymer Chemistry 42:624-638 (2004) and Landers et al., “Desktop Manufacturing of Complex Objects, Prototypes and Biomedical Scaffolds by Means of Computer-assisted Design Combined with Computer-guided 3D Plotting of Polymers and Reactive Oligomers,” Macromolecular Materials and Engineering 282:17-21 (2000). In addition, none of these systems explicitly measures the properties of, and monitors and controls the conditions experienced by the fabrication materials, the fabrication substrate, and the article under construction before, during, and/or after fabrication as an intrinsic part of the fabrication process and manufacturing plan. The fabrication process is thus limited to the spatial control of material placement on relatively simple, passive substrates. Temporal control of the evolution of material properties is therefore not possible, and complex substrates whose state must be controlled and monitored continuously are not readily accommodated. Fabricating into or onto substrates, such as living organisms or devices which must remain in operation continuously, is problematic.
A major challenge in orthopaedic tissue engineering is the generation of seeded implants with structures that mimic native tissue, both in terms of anatomic geometries and intratissue cell distributions. Previous studies have demonstrated that techniques such as injection molding (Chang et al., “Injection Molding of Chondrocyte/Alginate Constructs in the Shape of Facial Implants,” J. Biomed. Mat. Res. 55:503-511 (2001)) and casting (Hung et al., “Anatomically Shaped Osteochondral Constructs for Articular Cartilage Repair,” J. Biomech. 36:1853-1864 (2003)) of hydrogels can generate cartilage tissue in complex geometries. Other studies have investigated methods to reproduce regional variations in articular cartilage constructs by depositing multiple layers of chondrocytes (Klein et al., “Tissue Engineering of Stratified Articular Cartilage from Chondrocyte Subpopulations,” Osteoarthritis Cartilage 11:595-602 (2003)) or chondrocyte-seeded gels (Kim et al., “Experimental Model for Cartilage Tissue Engineering to Regenerate the Zonal Organization of Articular Cartilage,” Osteoarthritis Cartilage 11:653-664 (2003)). However, there remains no viable strategy for rapidly producing implants with correct anatomic geometries and cell distributions. Recently, advances in SFF techniques have enabled the deposition of multilayered structures composed of multiple chemically active materials (Malone et al., “Freeform Fabrication of 3D Zinc-Air Batteries and Functional Electro-Mechanical Assemblies,” Rapid Prototyping Journal 10:58-69 (2004)). Applicants believe that this technology has the potential to be adapted to the fabrication of living tissue under conditions that preserve cell viability.
The present invention is directed at overcoming disadvantages of prior art approaches and satisfying the need to establish a robust and reliable SFF system and method.